What every physician needs to know:

Pneumonia is inflammation and consolidation of lung tissue due to an infectious agent. It is the 8th leading cause of death in the US and it causes the highest morbidity and mortality at the extremes of age. The Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines define pneumonia as a new lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin which includes new onset of fever, purulent sputum, leukocytosis and a decline in oxygenation. Infections are often categorized as community-acquired pneumonia (CAP) versus hospital-acquired pneumonia (HAP) in order to tease out which patient populations are at risk for multi-drug resistant (MDR) organisms.

Among patients with hospital-acquired infections, HAP is the leading cause of death and causes 22% of all hospital-acquired infections. Ventilator- associated pneumonia (VAP) is defined as pneumonia that occurs >48 hours after intubation. HAP and VAP are associated with a great degree of morbidity and mortality. 52% of patients with HAP develop serious complications such as respiratory failure, pleural effusions, septic shock, renal failure and empyema. Mortality in non-ICU patients with HAP has been reported to be 26%. In the ICU, the mortality rate of HAP approaches 36% which is similar to the mortality rate for patients with VAP.

Classification:

The 2016 guidelines define HAP as pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission. The guidelines distinguish HAP from VAP which occurs 48 hours after endotracheal intubation.

In addition to defining HAP and VAP, the 2005 IDSA/ATS guidelines categorized healthcare associated pneumonia (HCAP) as a distinct entity from CAP. In recent years, given the increasing burden of chronic illnesses and the aging population, there was a concern that these patients who had frequent contact with the healthcare industry, were at higher risk for infection with MDR pathogens. In response to this, the 2005 IDSA/ATS guidelines defined HCAP as pneumonia that occurred in patients who were hospitalized for >48 hours in the last 90 days, resided in a nursing home or extended care facility, had undergone chronic dialysis within the last month or received IV antibiotics, or had chemotherapy or home wound care within the past 30 days. The goal was to identify patients with HCAP, HAP and VAP since it was thought that these hosts were at increased risk for MDR infections. At first glance, the patients at risk for HCAP resembled patients at risk for CAP since they presented to the emergency room from the community; however, their recent or frequent encounters with the healthcare system put them at risk for pathogens more likely to be encountered in the HAP or VAP patient population.

More recent data has shown that not all patients meeting criteria for HCAP are at increased risk for MDR pathogens and there is no evidence that treating these patients for MDR pathogens leads to improved outcomes. Thus the 2016 IDSA/ATS guidelines did not include HCAP. It is now suggested that risk factors for MDR organisms should be reviewed on a case-by-case basis to determine the antibiotic coverage needed. Risk factors for MDR pathogens e.g., recent antibiotic use, comorbidities, functional status and severity of illness should be assessed.

Are you sure your patient has hospital-acquired pneumonia? What should you expect to find?

Clinical features of HAP are indistinguishable from other forms of pneumonia. Patients will often present with cough, pleuritic chest pain, dyspnea and sputum production. Less specific symptoms include fevers, rigors, chills and fatigue. Other less common features are headache, nausea, vomiting, diarrhea and myalgias.

For CAP, 80% of patients have fevers and 45-70% of patients have tachypnea. One study demonstrated a negative likelihood ratio of 0.18 for the diagnosis of pneumonia if heart rate, respiratory rate and temperature were normal. If the prevalence of pneumonia is 5% in the population, a patient with normal vital signs would have a <1% probability of pneumonia. Tachypnea and tachycardia may be a more sensitive sign of pneumonia in older adults who are less likely to have increases in temperature. The elderly population is also more at risk for mental status changes which may be an indication of an underlying infection such as pneumonia.

On exam if there is consolidation in the lungs, dullness to percussion and increased tactile fremitus may be felt over the area of consolidation. On auscultation, crackles are found in 80% of patients with pneumonia. Whispered pectoriloquy, an increased loudness of a whisper, and egophony, an increased resonance or nasal quality of sounds, may be present in patients with pneumonia. Although these findings are helpful, there is no single exam finding that can rule in or out pneumonia.

In order to definitely diagnose pneumonia, a CXR is considered the gold standard. An opacity on CXR can represent pneumonia but should be interpreted with the history/physical in mind as the abnormality could also be related to pulmonary edema, blood, malignancy or inflammation.

Beware: there are other diseases that can mimic healthcare-associated pneumonia

It is important to consider other diagnoses when considering HAP. Atelectasis, CHF, ARDS, pulmonary embolus with infarction, pulmonary hemorrhage, lung contusion (from trauma), and aspiration pneumonitis can all mimic pneumonia. The 2016 IDSA/ATS guidelines recommend that clinical criteria with a new lung infiltrate be used to diagnosis HAP; however, as mentioned above, the clinical findings are nonspecific. Clinical criteria include new onset fever, leukocytosis, hypoxia and purulent sputum. When assessing the accuracy of different clinical criteria to diagnose VAP, one study showed that the presence of a new or progressive infiltrate plus ≥2 clinical features, either fever, leukocytosis or purulent sputum, resulted in a 69% sensitivity and 75% specificity for the diagnosis of pneumonia. The clinical pulmonary infection score (CPIS) which includes the previously mentioned clinical criteria plus oxygenation and tracheal aspirate has not been shown to be superior to conventional clinical criteria. Non-invasive and invasive sampling techniques have diagnostic values comparable to clinical criteria.

How and/or why do patients develop hospital-acquired pneumonia?

Pneumonia occurs due to microaspiration of oral flora. Forty-five percent of healthy adults aspirate during sleep and the incidence of aspiration increases in the chronically ill and elderly population. Seventy-five percent of severely ill patients become colonized with hospital flora within 48 hours of admission. These patients are at risk for aspirating oral flora and causing pneumonia with hospital-acquired organisms which tend to be more resistant than community acquired ones. HAPs/VAPs are composed of nosocomial pathogens including gram positive bacteria e.g., Staphylococcus aureus and Streptococcus pneumoniae as well as gram negative bacilli e.g., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp and Acinetobacterspp.

Which individuals are at greatest risk of developing MDR hospital-acquired pneumonia?

Aspiration is a major risk factor for HAP/VAP. When supine, the head of the bed should be elevated at 30-45° which has been shown to prevent aspiration and the subsequent development of pneumonia. The use of medications to increase the gastric pH has also been identified as a risk factor for HAP. Other risk factors include age >55 years, chronic lung disease, depressed consciousness, malnutrition, chronic renal failure, anemia and previous hospitalization.

Most of the evidence for risk factors for MDR pathogens stems from the VAP literature. Risk factors for MDR in VAP include use of IV antibiotics in the past 90 days, ≥5 days of hospitalization prior to occurrence of pneumonia, septic shock at time of pneumonia, ARDS before pneumonia and renal replacement therapy prior to pneumonia. Additionally, one should be aware of susceptibility patterns of nosocomial pathogens within their hospital based on the antibiogram. An ICU with >10% of Gram negative isolates resistant to monotherapy and with >10-20% of MRSA places patients at risk for MDR pathogens. The antibiogram is a useful tool to help inform providers about appropriate antibiotic use.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

Pneumonia is suspected in a patient with new changes on CXR with a clinical constellation of fever, leukocytosis and purulent sputum with a decline in oxygenation. The diagnosis of pneumonia is based on clinical evidence and radiographic findings, not laboratory evidence; however, lab studies can be used to support or refute the clinical assessment. Specifically, a CBC is important when assessing a patient for HAP. Leukocytosis or leukopenia, while nonspecific for pneumonia, can be used to support an infectious etiology such as pneumonia.

The IDSA/ATS guidelines recommend non-invasive sputum sampling, such as endotracheal aspirate to diagnose HAP rather than invasive sampling such as bronchoscopy. They also recommend against using procalcitonin, C-reactive protein, and CPIS score for diagnosis.

The evidence for blood cultures is controversial. 15% of VAP patients are bacteremic so prior guidelines did recommend obtaining blood cultures in suspected VAP patients. The evidence for blood cultures in HAP patients is even more limited as only a minority of patients are bacteremic. Blood cultures, however, may provide further guidance for treatment and de-escalation of organism specific antibiotic therapy.

What imaging studies will be helpful in making or excluding the diagnosis of HAP?

Imaging studies to aid in the diagnosis or exclusion of HAP include:

Chest radiographs

CT

Chest ultrasound (US)

CXRs are the mainstay for the radiographic diagnosis of HAP but chest CT and US are becoming more common. Much of the utility of CXRs centers around its convenience. CXR can be performed without transporting the patient off the ward, it is rapidly interpreted and is capable of identifying complications from pneumonia such as parapneumonic effusions. An absence of imaging abnormalities should lead the clinician to consider an alternative diagnosis.

CT of the chest is frequently utilized as an adjunctive modality for evaluation of pneumonia. A CT allows for more detailed visualization of the lung fields and localization of abnormal findings which may provide diagnostic clues. For example, an interstitial pattern may lead the clinician to consider viral or atypical pathogens as compared to a consolidative pattern that may suggest typical bacterial pathogens as the etiology. Additionally CT scans of the chest can help identify specific regions of the lungs that one may want to perform invasive sampling as outlined below.

Chest US is a newly utilized modality for imaging the lung parenchyma. Recent studies have demonstrated that bedside US of the chest is equivalent to CXR for the diagnosis of CAP in skilled users and data suggests it is equally sensitive for HAP. This modality can also identify complications of pneumonia and distinguish between consolidation and pulmonary edema. Bedside US, like a CXR is portable and provides rapid diagnostic information for the user; however, the user must be skilled at both performing and interpretation of the images.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of HAP?

N/A.

What diagnostic procedures will be helpful in making or excluding the diagnosis of HAP?

Bacterial culture is considered the gold standard for confirmation of pneumonia. Cultures can be obtained from sputum, nasotracheal suction, bronchoscopy or blood cultures. Pneumonia can be complicated by pleural effusions and empyemas and a thoracentesis can reveal an infected pleural space consistent with a parapneumonic effusion.

The diagnostic utility of sputum culture varies as oral and tracheal contamination can lead to false positive results, especially in patients with chronic lung diseases or chronic tracheostomy. HAP is not always due to bacterial infection and a negative sputum culture does not rule out HAP. Viral oropharyngeal swabs can be considered in the appropriate clinical context.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of HAP?

The diagnosis of pneumonia by sputum culture can be delayed due to the time needed for bacteria growth in vitro. Rapid detection of infectious organisms can lead to more appropriate delivery of empiric antibiotic therapy to the patients. Multiplex polymerase chain reaction of sputum samples is currently being tested as a potential means of rapid identification of bacteria, but test performance remains poor compared to conventional microbiologic cultures.

If you decide the patient has HAP, how should the patient be managed?

Once you have decided your patient has HAP, the clinician should take into consideration the following treatment pearls:

Establish need for respiratory or hemodynamic support for unstable patients

If risk for mortality is high, treat with two antipseudomonal antibiotics from different classes.

Consider empiric treatment as above during initial treatment, especially if microbiologic studies are pending. De-escalate and narrow antibiotics according to culture identification of microorganisms and their sensitivities.

Pneumonia is associated with complications such as acute respiratory failure and septic shock. Ensuring patients with HAP have adequate support to maintain oxygenation and ventilation and a mean arterial blood pressure sufficient to perfuse vital organs is paramount.

After stabilizing potentially critically ill patients, microbiology cultures of the blood and sputum should be obtained. The acquisition of sputum and blood cultures prior to the administration of antimicrobial therapy is preferred. Collecting cultures after administration of antibiotics may lead to less false negative culture results; however, delaying appropriate antimicrobial therapy for the collections of blood and sputum cultures is not recommended.

Antibiotic therapy should be tailored towards the most likely pathogenic organism(s) that depends on the clinical characteristics of the patient. One should consider data provided by prior cultures, antibiotic resistant patterns in the patient and local antibiograms. Recent HAP guidelines outline the treatment strategy and categorize patients based on risk of mortality and risk of MRSA (Table I). High-risk of MRSA infection is considered in patients with prior antibiotic use within past 90 days, admission to a hospital with S. aureus isolates positive for MRSA >20% while high-risk mortality is defined as need for ventilatory support or septic shock.

Table I.

Adopted from Kalil et al. Empiric antibiotic choice based on risk of mortality and infection with MRSA.

All patients should be empirically treated with antibiotics that have antipseudomonal and other gram-negative activity such as pipercillin-tazobactam, cefepime, levofloxacin or a carbapenem. If the patient is not high-risk for mortality but has an increased risk of MRSA, an anti-MRSA antibiotic should be added, such as vancomycin or linezolid. In patients at high risk for mortality or who have received IV antibiotics within the past 90 days, two antipseudomonal (not from same class) and an anti-MRSA antibiotic should be started empirically.

An important aspect of HAP treatment is the timely and appropriate de-escalation of empiric antibiotics. Although clinical scoring systems are not recommended in the decision process for the initiation or withholding of empiric antibiotic coverage, the modified clinical pneumonia severity index and serial procalcitonins can aid in antibiotic narrowing or discontinuing empiric treatment. A modified clinical pneumonia severity index score <6 or a low level of procalcitonin in patients with a clinical diagnosis of pneumonia indicate bacterial pneumonia is less likely. In these circumstances, a short course of treatment, as little as three days, can be considered.

What other considerations exist for patients with HAP?

Patients who meet diagnostic criteria for pneumonia may not have an infectious etiology for their symptoms. Acute exacerbations of inflammatory lung diseases can mimic clinical pneumonia. Input from a pulmonologist in patients with inflammatory lung diseases is advised. Patients who present with recurrent, non-resolving pneumonia should be considered for possible malignancy as the etiology for their symptoms.

Table I is adapted from Kalil et al. Empiric antibiotic choice based on risk of mortality and infection with MRSA. High-risk mortality includes ventilator-dependent respiratory failure or septic shock. High-risk MRSA includes prior culture positive for MRSA, > 20% S. aureus isolated as MRSA in the unit, or IV antibiotic exposure within the prior 90 days. MRSA: methicillin-resistant Staphylococcus aureus.